A5034887117- Melanoma and MAPK Pathways
- Cancer Research and Treatments
- Cancer Immunotherapy and Biomarkers
- Mechanisms of cancer metastasis
- Cancer Genomics and Diagnostics
- Immunotherapy and Immune Responses
- Respiratory viral infections research
- Influenza Virus Research Studies
- Cytokine Signaling Pathways and Interactions
- Immune cells in cancer
- Ferroptosis and cancer prognosis
- interferon and immune responses
- Glioma Diagnosis and Treatment
- Cancer Cells and Metastasis
- Angiogenesis and VEGF in Cancer
- vaccines and immunoinformatics approaches
- Cutaneous Melanoma Detection and Management
- Nanoplatforms for cancer theranostics
- Cancer-related molecular mechanisms research
- Cancer-related Molecular Pathways
- Chemokine receptors and signaling
- Mathematical Biology Tumor Growth
- Cancer, Lipids, and Metabolism
- Epigenetics and DNA Methylation
- Glycosylation and Glycoproteins Research
APLA Health
2022-2025
University of California, Los Angeles
2016-2024
UCLA Jonsson Comprehensive Cancer Center
2024
Immune checkpoint blockade (ICB) with PD-1/PD-L1 inhibition has revolutionized the treatment of non-small cell lung cancer (NSCLC). Durable responses, however, are observed only in a subpopulation patients. Defective antigen presentation and an immunosuppressive tumor microenvironment (TME) can lead to deficient T recruitment ICB resistance. We evaluate intratumoral (IT) vaccination CXCL9- CXCL10-engineered dendritic cells (CXCL9/10-DC) as strategy overcome IT CXCL9/10-DC leads enhanced...
Chronic inflammation facilitates tumor progression. We discovered that a subset of non-small cell lung cancer cells underwent gradually progressing epithelial-to-mesenchymal (EMT) phenotype following 21-day exposure to IL-1β, an abundant proinflammatory cytokine in the at-risk for pulmonary and microenvironments. Pathway analysis gene expression profile vitro functional studies revealed EMT EMT-associated phenotypes, including enhanced invasion, PD-L1 upregulation, chemoresistance, were...
Abstract LKB1 inactivating mutations are commonly observed in patients with KRAS-mutant non–small cell lung cancer (NSCLC). Although treatment of NSCLC immune checkpoint inhibitors (ICI) has resulted improved overall survival a subset patients, studies have revealed that co-occurring KRAS/LKB1 drive primary resistance to ICIs NSCLC. Effective therapeutic options overcome ICI LKB1-mutant limited. Here, we report loss results increased secretion the C–X–C motif (CXC) chemokines an NH2-terminal...
Focal amplifications (FA) can mediate targeted therapy resistance in cancer. Understanding the structure and dynamics of FAs is critical for designing treatments that overcome plasticity-mediated resistance. We developed a melanoma model dual MAPK inhibitor (MAPKi) bears BRAFV600 through either extrachromosomal DNA (ecDNA)/double minutes (DM) or intrachromosomal homogenously staining regions (HSR). Cells harboring BRAFV600E displayed mode switching between DMs HSRs, from both de novo genetic...
Background Despite recent advances in immunotherapy, many patients with non-small cell lung cancer (NSCLC) do not respond to immune checkpoint inhibitors (ICI). Resistance ICI may be driven by suboptimal priming of antitumor T lymphocytes due poor antigen presentation as well their exclusion and impairment the immunosuppressive tumor microenvironment (TME). In a phase I trial NSCLC, situ vaccination (ISV) dendritic cells engineered secrete CCL21 (CCL21-DC), chemokine that facilitates...
Abstract Poly-adenosine diphosphate (ADP)-ribose polymerase 7 (PARP7) is an enzyme that postranslationally modifies target proteins with ADP-ribose group, which required for multiple cellular processes, including DNA repair, immune function, and metabolism. Recent studies have identified a subset of non-small cell lung cancer (NSCLC) exhibiting dependency to PARP7, suggesting PARP7 may be therapeutic NSCLC. In addition, was recently as evasion mechanism cells escape surveillance by dampening...
Abstract Despite recent advances in immunotherapy with immune checkpoint inhibitors, many patients non–small cell lung cancer (NSCLC) fail to respond or develop resistance after an initial response. In situ vaccination (ISV) engineered viruses has emerged as a promising antigen-agnostic strategy that can both condition the tumor microenvironment and augment antitumor T-cell responses overcome resistance. We live attenuated viral vaccine, hyper–IFN-sensitive (HIS) virus, by conducting...
Abstract Lung cancer is the leading cause of related deaths worldwide, with most prevalent subtype being non-small cell lung (NSCLC). As only a subset patients exhibits durable clinical responses to current treatments, including targeted therapy and immunotherapy, new treatment options are needed. Integrins (ITGs) diverse class heterodimeric, transmembrane receptors that bind extracellularly extracellular matrix (ECM) intracellularly cytoskeleton integrate signals bi-directionally between...
Abstract A major hurdle in treatment of Non-Small Cell Lung Cancer (NSCLC) with anti-PD-1 immune checkpoint blockade (ICB) therapy is a lack response (primary resistance) and relapse after an initial (acquired resistance). Recent studies reveal that responses to PD-1/PD-L1 are associated high tumor mutational burden (TMB), increased CD8+ T cell infiltration baseline PD-L1 expression within the microenvironment (TME), while impaired antigen presentation immunosuppressive TME have been...
Abstract Lung cancer remains the deadliest form of cancer, claiming 1.8 million lives worldwide in 2020. While treatment options have improved with advent immune checkpoint inhibitors (ICI), many patients do not respond to immunotherapy or develop resistance following initial response. A significant subset non-small cell lung (NSCLC) harbors somatic co-mutations Kirsten rat sarcoma virus (KRAS) and Liver kinase 1 [LKB1, also known as serine/threonine 11 (STK11)] genes, whose tumors are...
<p>Primer sequences for real-time PCR</p>
<p>In vitro studies with Irf3KO 1940A-KPL, B16F10-ΔS, B16F10-ΔL, B16F10-Jak2KO, B16F10-Jak1KO cell lines</p>
<p>Flow antibodies and Fixable Viability dye</p>
<p>In vitro cell viability assay and the safety profile of HIS</p>
<p>HIS inhibits NSCLC tumors growth in mice</p>
<div>Abstract<p>Despite recent advances in immunotherapy with immune checkpoint inhibitors, many patients non–small cell lung cancer (NSCLC) fail to respond or develop resistance after an initial response. <i>In situ</i> vaccination (ISV) engineered viruses has emerged as a promising antigen-agnostic strategy that can both condition the tumor microenvironment and augment antitumor T-cell responses overcome resistance. We live attenuated viral vaccine,...
<p>Gating strategy for flow cytometry and supplementary scRNA-seq data</p>
<p>Assessment of synergy and flow phenotyping immune cells following combination therapy</p>
Abstract Cancer cells display two modes of focal amplifications (FAs), extrachromosomal DNA/double-minutes (ecDNA/DMs) and intrachromosomal homogenously staining regions (HSRs). Understanding the plasticity these is critical for preventing targeted therapy resistance. We developed a combined BRAF plus MEK inhibitor resistance melanoma model that bears high through both DM HSR modes, investigated FA dynamics in context drug plasticity. Cells harboring FAs displayed mode switching between DMs...
Abstract Lung cancer is the most common cause of death worldwide with approximately 85% patients having non-small cell lung (NSCLC). Checkpoint blockade immunotherapy has evolved current treatment landscape robust and durable responses in 20% progressive, locally advanced or metastatic NSCLC, as well treatment-naïve disease. Inefficient tumor antigen presentation, diminished T infiltration into LKB1-inactivating mutations contribute to mechanisms resistance programmed death-ligand 1 (PD-L1)...
Abstract Cancer cells display two modes of focal amplifications (FA): extrachromosomal double minutes (DMs/ecDNAs) and intrachromosomal homogenously staining regions (HSRs). Understanding the plasticity these is critical for preventing targeted therapy resistance. We developed a combined BRAF plus MEK inhibitor resistance melanoma model that bears high through both ecDNA HSR modes, investigated FA dynamics in context drug plasticity. Cells harboring FAs displayed mode switching between...
Abstract BRAF kinase is a key intermediate in the MAP pathway, which associated with cell growth and proliferation. BRAFV600E activating mutation found 50-60% of all melanomas 7% cancer malignancies. Despite an unprecedented initial response, patients treated highly effective inhibitor, vemurafenib (FDA approved 2011), can acquire drug resistance as little 6-9 months. Epigenetically driven epithelial-to-mesenchymal transition (EMT), hallmark stem-like cells (CSCs), potential mechanism that...
Abstract Treatment for non-small cell lung cancer (NSCLC) has been transformed by the use of immune checkpoint inhibitors (ICIs), which promote ability system to attack cells. Resistance these therapies thus represents a major barrier effectively treating patients with NSCLC. Tumor heterogeneity identified as an important factor that may mediate ICI resistance, and prior analyses NSCLC tumors have accordingly shown greater tumor is correlated diminished response ICIs. However, exact...
<div>Abstract<p>Focal amplifications (FA) can mediate targeted therapy resistance in cancer. Understanding the structure and dynamics of FAs is critical for designing treatments that overcome plasticity-mediated resistance. We developed a melanoma model dual MAPK inhibitor (MAPKi) bears <i>BRAF</i><sup>V600</sup> through either extrachromosomal DNA (ecDNA)/double minutes (DM) or intrachromosomal homogenously staining regions (HSR). Cells harboring...